The specific activities of four of the key enzymes of rough and smooth macrosomes, isolated from endoplasmic reticulular membranes of rat liver and kidney have been measured during the neonatal and early weaning periods of rapid membrane proliferation. The activities of sn-glycerol-3 phosphate acyltransferase, NADPH-cytochrome-c reductase and nucleoside diphosphatase remain parallel in the rough and smooth microsomes during post natal changes in the quantity of enzyme, the rough membranes showing somewhat more activity. This is accord with a picture of enzymes, newly synthesized on ribosome-bearing membranes, being rapidly distributed to the smooth membranes. On the other hand, glucose-6-phosphatase showed non-parallel changes with age in the rough and smooth membranes the well established neonatal overshoot in activity being almost entirely due to changes in the enzyme in the rough ER. The enzyme activity in the RER reaches a maximum and then decreases after day 2 while that in the smooth membrane is still slowly increasing. It appears that lateral diffusion of glucose-7-phosphatase along the membrane is proceeding at a slower rate than is its replacement by synthesis and degradation within the developing membranes of the neonatal liver.